tbuckley/cabot-search huggingface dataset:
Reply to A. Abner et al
Authors: Ting Martin, Yilun Sun, Daniel E. Spratt, Amar U. Kishan
Journal: Journal of Clinical Oncology (2023)

We thank Abner and Vicini 1 for their correspondence in response to our article. 2We agree that those performing meta-analyses and pooled analyses must take measures to account for important limitations inherent to evaluating heterogeneous data sets.However, we disagree with several of the statements made by Abner et al, such as ascribing potential survival benefits observed in this analysis to substantial progress in the delivery of radiation therapy.When interpreting and contextualizing our results, it is important to examine the totality of the randomized evidence in prostate cancer and to carefully consider the nuances of the difference between unadjusted and inverse probability treatment weighting (IPTW) adjusted analyses.First, it is important to note that two phase III randomized trials (NRG/Radiation Therapy Oncology Group 9413 3,4 and Ottawa 0101 5 ) have evaluated the sequencing of androgen-deprivation therapy (ADT), rather than the single trial that is mistakenly referenced by Abner et al.Both trials suggested a potentially important impact for ADT sequencing with prostateonly radiation therapy (PORT).In fact, an individual patient data (IPD) meta-analysis 6 on the basis of these two trials also demonstrated that multiple outcomes, including progression-free survival, biochemical recurrence, distant metastasis (DM), and metastasis-free survival, were all significantly improved in patients treated with adjuvant ADT.That study was not subject to the forms of bias implied by the authors, given it was purely based on randomized evidence from ADT sequencing.The fact that two randomized trials from two different countries, 3-5 a pooled analysis of the two trials, 6 and the SANDSTORM meta-analysis 2 all numerically or significantly favored adjuvant ADT in the setting of PORT lends strong credence to the validity of this effect.None showed any potential benefit of neoadjuvant ADT with PORT.
Antimicrobial peptides for combating drug-resistant bacterial infections
Authors: Jiaqi Xuan, Weiguo Feng, Jiaye Wang, Ruichen Wang, Bowen Zhang, Letao Bo, Zhe-Sheng Chen, Hui Yang, Leming Sun
Journal: Drug Resistance Updates (2023)

The problem of drug resistance due to long-term use of antibiotics has been a concern for years. As this problem grows worse, infections caused by multiple bacteria are expanding rapidly and are extremely detrimental to human health. Antimicrobial peptides (AMPs) are a good alternative to current antimicrobials with potent antimicrobial activity and unique antimicrobial mechanisms, which have advantages over traditional antibiotics in fighting against drug-resistant bacterial infections. Currently, researchers have conducted clinical investigations on AMPs for drug-resistant bacterial infections while integrating new technologies in the development of AMPs, such as changing amino acid structure of AMPs and using different delivery methods for AMPs. This article introduces the basic properties of AMPs, deliberates the mechanism of drug resistance in bacteria and the therapeutic mechanism of AMPs. The current disadvantages and advances of AMPs in combating drug-resistant bacterial infections are also discussed. This article provides important insights into the research and clinical application of new AMPs for drug-resistant bacterial infections.
SpineRegNet: Spine Registration Network for volumetric MR and CT image by the joint estimation of an affine-elastic deformation field
Authors: Lei Zhao, Shumao Pang, Yangfan Chen, Xiongfeng Zhu, Ziyue Jiang, Zhihai Su, Hai Lu, Yujia Zhou, Qianjin Feng
Journal: Medical Image Analysis (2023)
Improved outcomes for relapsed/refractory Hodgkin lymphoma after autologous transplantation in the era of novel agents
Authors: Michael A Spinner, R. Alejandro Sica, John S Tamaresis, Ying Lu, Cheryl Chang, Robert Lowsky, Matthew J. Frank, Laura J Johnston, David B Miklos, Lori Muffly, Robert S. Negrin, Andrew R. Rezvani, Parveen Shiraz, Judith A. Shizuru, Wen-Kai Weng, Michael S. Binkley, Richard T. Hoppe, Ranjana H Advani, Sally Arai
Journal: Blood (2023)

The treatment landscape of relapsed/refractory (R/R) classic Hodgkin lymphoma (cHL) has evolved significantly over the past decade following the approval of brentuximab vedotin (BV) and the programmed death-1 (PD-1) inhibitors. We evaluated how outcomes and practice patterns have changed for R/R cHL patients who underwent autologous hematopoietic cell transplantation (AHCT) at our institution from 2011-2020 (N=183) compared to 2001-2010 (N=159) and evaluated prognostic factors for progression-free survival (PFS) and overall survival (OS) in both eras. OS was superior in the modern era (4-year estimates 89.1% vs 79.0%, HR 0.53, 95% CI 0.33-0.85, p=0.011) with a trend towards lower non-relapse mortality beyond 2 years post-transplant. Among patients who progressed after AHCT, 4-year post-progression survival increased from 43.3% to 71.4% in the modern era, reflecting increasing use of BV and the PD-1 inhibitors. In multivariable analysis for patients transplanted in the modern era, age ³45 years, primary refractory disease, and lack of complete remission pre-AHCT were associated with inferior PFS, while receipt of a PD-1 inhibitor-based regimen pre-AHCT was associated with superior PFS (HR 0.21, 95% CI 0.05-0.80, p=0.030). Extranodal disease at relapse was associated with inferior OS (HR 3.12, 95% CI 1.25-7.77, p=0.014). Our study demonstrates improved survival for R/R cHL after AHCT in the modern era attributed to more effective salvage regimens allowing for better disease control pre-AHCT and improved outcomes for patients who progressed after AHCT. Excellent outcomes were observed with PD-1 inhibitor-based salvage regimens pre-AHCT and support a randomized trial evaluating immunotherapy in the second line setting.
A response to claims of emergent intelligence and sentience in a dish
Authors: Fuat Balci, Suliann Ben Hamed, Thomas Boraud, Sébastien Bouret, Thomas Brochier, Cédric Brun, Jeremiah Y. Cohen, Etienne Coutureau, Marc Deffains, Valérie Doyère, Georgia G. Gregoriou, J. Alexander Heimel, Bjørg Elisabeth Kilavik, Daeyeol Lee, Eric C. Leuthardt, Zachary F. Mainen, Mackenzie Mathis, Ilya E. Monosov, Jérémie Naudé, Amy L. Orsborn, Camillo Padoa-Schioppa, Emmanuel Procyk, Bernardo Sabatini, Jérôme Sallet, Carmen Sandi, Jeffrey D. Schall, Alireza Soltani, Karel Svoboda, Charles R.E. Wilson, Jan Zimmermann
Journal: Neuron (2023)
<i>De Novo</i> Generation of Pulmonary Ionocytes from Normal and Cystic Fibrosis Human Induced Pluripotent Stem Cells
Authors: Ruobing Wang, Chantelle Simone-Roach, Jonathan Lindstrom-Vautrin, Feiya Wang, Stuart Rollins, Pushpinder Singh Bawa, Junjie Lu, Yang Tang, Mary Lou Beermann, Thorsten Schlaeger, John Mahoney, Steven M. Rowe, Finn J. Hawkins, Darrell N. Kotton
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"De Novo Generation of Pulmonary Ionocytes from Normal and Cystic Fibrosis Human Induced Pluripotent Stem Cells." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp. –
Sensitivity and specificity of two investigational Point of care tests for Syphilis and HIV (PoSH Study) for the diagnosis and treatment of infectious syphilis in Canada: a cross-sectional study
Authors: Ameeta E. Singh, Noel Ives, Jennifer Gratrix, Carla Vetland, Leslie Ferron, Megan Crawford, Lisa Hale-Balla, Kathryn Dong, Garret Meyer, Petra Smyczek, Rick Galli, Sean B. Rourke, Kevin Fonseca
Journal: Clinical Microbiology and Infection (2023)

Single-visit testing and treatment for syphilis can reduce follow-up visits. The objectives of this study were to evaluate the performance and treatment outcomes of two dual syphilis/HIV point-of-care tests (POCTs).Participants aged 16 years and older were offered concurrent syphilis/HIV POCTs with fingerstick blood sampling using two extremely rapid (<5 minutes) devices (MedMira Multiplo Rapid TP/HIV test and INSTI Multiplex HIV-1/HIV-2/Syphilis Antibody Test). Those with positive POCT results were offered same-day syphilis treatment and linkage to HIV care. Nurses performed testing at two emergency departments, a First Nations community, a correctional facility, and a sexually transmitted infection clinic. POCT results were compared with those of standard serological testing. Sensitivity and specificity were calculated.Between August 2020 and February 2022, 1526 visits were completed. Both POCTs accurately identified participants with HIV (sensitivity, 100% [24 of 24]; 95% CI, 86.2-100%; specificity, 99.6% [1319 of 1324]; 95% CI, 99.1-99.8%), linking 24 HIV cases to care. Both tests were most sensitive with a rapid plasma reagin (RPR) of ≥1:8 dilutions (Multiplo: sensitivity, 98.3% [231 of 235]; 95% CI, 95.7-99.3%; specificity, 99.5% [871 of 875]; 95% CI, 98.8-99.8%; INSTI Multiplex: sensitivity, 97.9% [230 of 235]; 95% CI, 95.1-99.1%; specificity, 99.8% [873 of 875]; 95% CI, 99.2-99.9%) and least sensitive with non-reactive RPR (Multiplo: sensitivity, 54.1% [59 of 109]; 95% CI, 44.8-63.2%; specificity, 99.5% [871 of 875]; 95% CI, 98.8-99.8%; INSTI Multiplex: sensitivity, 28.4% [31 of 109]; 95% CI, 20.8-37.5%; specificity, 99.8% [873 of 875]; 95% CI, 99.2-99.9%). Eighty-five percent of participants with infectious syphilis were treated on the same day as the positive POCT result.Two extremely rapid (<5 minutes) dual syphilis/HIV POCTs showed excellent sensitivity and specificity for the diagnosis of active syphilis (RPR, ≥1:8 dilutions) and HIV and confirmed the ability to offer single-visit testing and treatment for syphilis and linkage to HIV care in diverse clinical settings.
Cryo-EM structure of coagulation factor V short
Authors: Bassem M. Mohammed, Leslie A Pelc, Michael J Rau, Enrico Di Cera
Journal: Blood (2023)

Coagulation factor V (fV) is the inactive precursor of fVa, an essential component of the prothrombinase complex required for rapid activation of prothrombin in the penultimate step of the coagulation cascade. In addition, fV regulates the tissue factor pathway inhibitor α (TFPIα) and protein C pathways that inhibit the coagulation response. A recent cryogenic electron microscopy (cryo-EM) structure of fV has revealed the architecture of its A1-A2-B-A3-C1-C2 assembly but left the mechanism that keeps fV in its inactive state unresolved due to intrinsic disorder in the B domain. A splice variant of fV, fV short, carries a large deletion of the B domain that produces constitutive fVa-like activity and unmasks epitopes for binding of TFPIα. The cryo-EM structure of fV short was solved at 3.2 Å resolution and reveals the arrangement of the entire A1-A2-B-A3-C1-C2 assembly for the first time. The shorter B domain stretches across the entire width of the protein, making contacts with the A1, A2 and A3 domains but suspended over the C1 and C2 domains. In the portion distal to the splice site, several hydrophobic clusters and acidic residues provide a likely binding site for the basic C-terminal end of TFPIα. In fV, these epitopes may bind intramolecularly the basic region of the B domain. The cryo-EM structure reported in this study advances our understanding of the mechanism that keeps fV in its inactive state, provides new targets for mutagenesis and facilitates future structural analysis of fV short in complex with TFPIα, protein S and fXa.
Phase II clinical trial evaluating Abatacept in patients with steroid-refractory chronic graft versus host disease
Authors: Anita G. Koshy, Haesook T. Kim, Jessica Liegel, Jon E. Arnason, Vincent T. Ho, Joseph H. Antin, Robin Joyce, Corey S. Cutler, Mahasweta Gooptu, Sarah Nikiforow, Emma K. Logan, Pavania Elavalakanar, Michele Narcis, Dina Stroopinsky, Zachary M. Avigan, Leora Boussi, Susan L Stephenson, Hassan El Banna, Poorva Bindal, Giulia Cheloni, David E. Avigan, Robert J. Soiffer, Jacalyn Rosenblatt
Journal: Blood (2023)
Refining the Definition of Stage 1 Type 1 Diabetes: An Ontology-Driven Analysis of the Heterogeneity of Multiple Islet Autoimmunity
Authors: Brigitte I. Frohnert, Mohamed Ghalwash, Ying Li, Kenney Ng, Jessica L. Dunne, Markus Lundgren, William Hagopian, Olivia Lou, Christiane Winkler, Jorma Toppari, Riitta Veijola, Vibha Anand, Anette G. Ziegler, Ezio Bonifacio, Peter Achenbach, Christiane Winkler, Marian Rewers, Brigitte I. Frohnert, Jill Norris, Andrea Steck, Kathleen Waugh, Liping Yu, William A. Hagopian, Michael Killian, Angela Wolf, Jocelyn Meyer, Claire Crouch, Jared Radtke, Åke Lernmark, Helena Elding Larsson, Markus Lundgren, Marlena Maziarz, Lampros Spiliopoulos, Josefin Jönsson, Riitta Veijola, Jorma Toppari, Jorma Ilonen, Mikael Knip, Vibha Anand, Mohamed Ghalwash, Kenney Ng, Zhiguo Li, B.C. Kwon, Harry Stravopolous, Eileen Koski, Ashwani Malhotra, Shelley Moore, Jianying Hu, Jessica Dunne, Bin Liu, Ying Li, Olivia Lou, Frank Martin
Journal: Diabetes Care (2023)

To estimate the risk of progression to stage 3 type 1 diabetes based on varying definitions of multiple islet autoantibody positivity (mIA).
Impact of Overnight Glucose on Next-Day Functioning in Adults With Type 1 Diabetes: An Exploratory Intensive Longitudinal Study
Authors: Elizabeth A. Pyatak, Donna Spruijt-Metz, Stefan Schneider, Raymond Hernandez, Loree T. Pham, Claire J. Hoogendoorn, Anne L. Peters, Jill Crandall, Haomiao Jin, Pey-Jiuan Lee, Jeffrey S. Gonzalez
Journal: Diabetes Care (2023)

OBJECTIVE While there is evidence that functioning, or ability to perform daily life activities, can be adversely influenced by type 1 diabetes, the impact of acute fluctuations in glucose levels on functioning is poorly understood. RESEARCH DESIGN AND METHODS Using dynamic structural equation modeling, we examined whether overnight glucose (coefficient of variation[CV], percent time &amp;lt;70 mg/dL, percent time &amp;gt;250 mg/dL) predicted seven next-day functioning outcomes (mobile cognitive tasks, accelerometry-derived physical activity, self-reported activity participation) in adults with type 1 diabetes. We examined mediation, moderation, and whether short-term relationships were predictive of global patient-reported outcomes. RESULTS Overall next-day functioning was significantly predicted from overnight CV (P = 0.017) and percent time &amp;gt;250 mg/dL (P = 0.037). Pairwise tests indicate that higher CV is associated with poorer sustained attention (P = 0.028) and lower engagement in demanding activities (P = 0.028), time &amp;lt;70 mg/dL is associated with poorer sustained attention (P = 0.007), and time &amp;gt;250 mg/dL is associated with more sedentary time (P = 0.024). The impact of CV on sustained attention is partially mediated by sleep fragmentation. Individual differences in the effect of overnight time &amp;lt;70 mg/dL on sustained attention predict global illness intrusiveness (P = 0.016) and diabetes-related quality of life (P = 0.036). CONCLUSIONS Overnight glucose predicts problems with objective and self-reported next-day functioning and can adversely impact global patient-reported outcomes. These findings across diverse outcomes highlight the wide-ranging effects of glucose fluctuations on functioning in adults with type 1 diabetes.
Modulating Temporospatial Phosphate Equilibrium by Nanoparticulate Mineralized Collagen Materials Induces Osteogenesis via PiT‐1 and PiT‐2
Authors: Xiaoyan Ren, Qi Zhou, Meiwand Bedar, David Foulad, Kelly X. Huang, Dillon Dejam, Natalie J. Dahan, Vasiliki Kolliopoulos, Brendan A.C. Harley, Justine C. Lee
Journal: Advanced Healthcare Materials (2023)

The temporospatial equilibrium of phosphate contributes to physiological bone development and fracture healing, yet optimal control of phosphate content has not been explored in skeletal regenerative materials. Nanoparticulate mineralized collagen glycosaminoglycan (MC-GAG) is a synthetic, tunable material that promotes in vivo skull regeneration. In this work, the effects of MC-GAG phosphate content on the surrounding microenvironment and osteoprogenitor differentiation are investigated. This study finds that MC-GAG exhibits a temporal relationship with soluble phosphate with elution early in culture shifting to absorption with or without differentiating primary bone marrow-derived human mesenchymal stem cells (hMSCs). The intrinsic phosphate content of MC-GAG is sufficient to stimulate osteogenic differentiation of hMSCs in basal growth media without the addition of exogenous phosphate in a manner that can be severely reduced, but not eliminated, by knockdown of the sodium phosphate transporters PiT-1 or PiT-2. The contributions of PiT-1 and PiT-2 to MC-GAG-mediated osteogenesis are nonredundant but also nonadditive, suggestive that the heterodimeric form is essential to its activity. These findings indicate that the mineral content of MC-GAG alters phosphate concentrations within a local microenvironment resulting in osteogenic differentiation of progenitor cells via both PiT-1 and PiT-2.
When ACL reconstruction does not help: risk factors associated with not achieving the minimal important change for the KOOS Sport/Rec and QoL
Authors: Janina Kaarre, Rebecca Simonson, Viktor Ris, Thorkell Snaebjörnsson, James J Irrgang, Volker Musahl, Kristian Samuelsson, Eric Hamrin Senorski
Journal: British Journal of Sports Medicine (2023)

To determine factors associated with not achieving a minimal important change (MIC) in the Knee injury and Osteoarthritis Outcome Score (KOOS) Function in Sport and Recreation (Sport/Rec), and Knee-Related Quality of Life (QoL) subscales 1 year after anterior cruciate ligament reconstruction (ACL-R).This study used data from the Swedish National Knee Ligament Registry. Multivariable logistic regression models were used to identify factors associated with not achieving a MIC. The change in the preoperative and postoperative KOOS Sport/Rec and QoL subscale scores were dichotomised based on not achieving MIC for both subscales versus achieving MIC for either one or both subscales. The MICs for the Sport/Rec and QoL subscales were 12.1 and 18.3, respectively, and were used to combine both subscales into a single variable (Sport & QoL).Of 16 131 included patients, 44% did not achieve the MIC for the combined Sport/Rec and QoL subscales 1 year after ACL-R. From the multivariable stepwise logistic regression, older patients (OR 0.91, 95% CI 0.88 to 0.94; p<0.0001), males (OR 0.93, 95% CI 0.87 to 0.99; p=0.034) and patients receiving hamstring tendon autograft ACL-R (OR 0.70, 95% CI 0.60 to 0.81; p<0.0001) had lower odds of not achieving the MIC 1 year after ACL-R compared with younger patients, females and patients receiving patellar tendon autograft. Furthermore, patients with cartilage injuries (OR 1.17, 95% CI 1.09 to 1.27; p<0.0001) and higher pre-operative KOOS Sport/Rec and QoL scores (OR 1.34, 95% CI 1.31 to 1.36; p<0.0001) had higher odds of not achieving the MIC.Younger patients, females and patients with cartilage injuries and higher pre-operative Sport/Rec and QoL KOOS scores are less likely to benefit from ACL-R and subsequently, have a lower probability for improved Sport/Rec and QoL scores after ACL-R. Furthermore, graft choice may also affect the risk of not achieving the MIC.Retrospective cohort study, level III.
Medication-Associated Diethylene Glycol Mass Poisoning — A Preventable Cause of Illness and Death
Authors: Joshua Schier, Arthur Chang, Vikas Kapil
Journal: New England Journal of Medicine (2023)

Gambia recently faced a medication-associated diethylene glycol mass poisoning — the latest of numerous such events over the past 80 years. Why do such tragedies continue to happen, and what can be done to prevent them?
CEP162 deficiency causes human retinal degeneration and reveals a dual role in ciliogenesis and neurogenesis
Authors: Nafisa Nuzhat, Kristof Van Schil, Sandra Liakopoulos, Miriam Bauwens, Alfredo Dueñas Rey, Stephan Käseberg, Melanie Jäger, Jason R. Willer, Jennifer Winter, Hanh M. Truong, Nuria Gruartmoner, Mattias Van Heetvelde, Joachim Wolf, Robert Merget, Sabine Grasshoff-Derr, Jo Van Dorpe, Anne Hoorens, Heidi Stöhr, Luke Mansard, Anne-Françoise Roux, Thomas Langmann, Katharina Dannhausen, David Rosenkranz, Karl M. Wissing, Michel Van Lint, Heidi Rossmann, Friederike Häuser, Peter Nürnberg, Holger Thiele, Ulrich Zechner, Jillian N. Pearring, Elfride De Baere, Hanno J. Bolz
Journal: Journal of Clinical Investigation (2023)

Defects in primary or motile cilia result in a variety of human pathologies, and retinal degeneration is frequently associated with these so-called ciliopathies. We found that homozygosity for a truncating variant in CEP162, a centrosome and microtubule-associated protein required for transition zone assembly during ciliogenesis and neuronal differentiation in the retina, caused late-onset retinitis pigmentosa in 2 unrelated families. The mutant CEP162-E646R*5 protein was expressed and properly localized to the mitotic spindle, but it was missing from the basal body in primary and photoreceptor cilia. This impaired recruitment of transition zone components to the basal body and corresponded to complete loss of CEP162 function at the ciliary compartment, reflected by delayed formation of dysmorphic cilia. In contrast, shRNA knockdown of Cep162 in the developing mouse retina increased cell death, which was rescued by expression of CEP162-E646R*5, indicating that the mutant retains its role for retinal neurogenesis. Human retinal degeneration thus resulted from specific loss of the ciliary function of CEP162.
Targeting CAFs to Improve Anti-PD-1 Checkpoint Immunotherapy
Authors: Daniele V.F. Tauriello
Journal: Cancer Research (2023)

Abstract The tumor microenvironment is a complex ecosystem that drives cancer progression and restrains immunity. Although immune checkpoint inhibitors have shown strong potential in a subset of patients, a better understanding of suppressive mechanisms may inspire ways to improve immunotherapeutic efficacy. A new study in this issue of Cancer Research focuses on targeting cancer-associated fibroblasts in preclinical models of gastric tumors. Aiming to rebalance anticancer immunity and enhance treatment responses to checkpoint-blocking antibodies, this work also addresses the potential for multitarget tyrosine kinase inhibitors in treating gastrointestinal cancer. See related article by Akiyama et al., p. 753
Acquiring tissue for advanced lung cancer diagnosis and comprehensive biomarker testing: A National Lung Cancer Roundtable best‐practice guide
Authors: Adam H. Fox, Mizuki Nishino, Raymond U. Osarogiagbon, M. Patricia Rivera, Lauren S. Rosenthal, Robert A. Smith, Farhood Farjah, Lynette M. Sholl, Gerard A. Silvestri, Bruce E. Johnson
Journal: CA A Cancer Journal for Clinicians (2023)

Abstract Advances in biomarker‐driven therapies for patients with nonsmall cell lung cancer (NSCLC) both provide opportunities to improve the treatment (and thus outcomes) for patients and pose new challenges for equitable care delivery. Over the last decade, the continuing development of new biomarker‐driven therapies and evolving indications for their use have intensified the importance of interdisciplinary communication and coordination for patients with or suspected to have lung cancer. Multidisciplinary teams are challenged with completing comprehensive and timely biomarker testing and navigating the constantly evolving evidence base for a complex and time‐sensitive disease. This guide provides context for the current state of comprehensive biomarker testing for NSCLC, reviews how biomarker testing integrates within the diagnostic continuum for patients, and illustrates best practices and common pitfalls that influence the success and timeliness of biomarker testing using a series of case scenarios.